UPREGULATED ARACHIDONIC ACID CASCADE IN BIPOLAR DISORDER BRAIN[unreadable] Bipolar disorder is characterized by recurrent manic and depressive episodes, but its etiology, pathophysiology and treatment mechanisms are not clear. Postmortem frontal cortex from 8 bipolar disorder patients compared with cortex from 6 age-matched controls had significant increases in a number of arachidonic (AA) cascade markers: cytosolic mRNA and protein levels of cytosolic phospholipase A2 and cyclooxygenase-2, and the respective AP-2 and NF-kB factors regulating transcription of these enzymes. These changes suggest the presence neuroinflammation and excitotoxicity in bipolar disorder, since we showed in animal models that both processes upregulate AA cascade markers (Rao et al. Abstr. Soc. Neurosci. 37, 707.5, 2007)[unreadable] [unreadable] HYPERGLUTAMATERGIC STATE IN BIPOLAR DISORDER BRAIN[unreadable] Postmortem frontal cortex from bipolar disorder patients, compared with control cortex, had significantly decreased mRNA and protein levels of two N-methyl-D-aspartate (NMDA) receptor subunits, NR1 and NR3A. Since such decreases increase NMDA signaling in experimental models, they suggest the presence glutamate-related hyperactivity in the bipolar disorder brain. Animal models of NMDA-induced excitotoxicity have elevated brain arachidonic acid (AA) metabolism, which may explain why mood stabilizers given to rats block NMDA receptor transmission involving arachidonic acid (Kim et al. Abstr. Soc Neurosci, 37, 707.704, 2007).[unreadable] [unreadable] DISTURBED G-PROTEIN MEDIATED NEUROTRANSMISSION IN BIPOLAR DISORDER [unreadable] G-proteins couple certain neuroreceptors to signaling enzymes, and are regulated by G-protein receptor kinases (GRKs). We reported that antibipolar agents upregulated rat brain expression of GRK3. In contrast, in the present study we found decreased protein and mRNA levels of G-protein subunits &#946; and &#947; and of GRK3 in postmortem frontal cortex from bipolar patients, compared with control tissue. The positive effects of mood stabilizers on GRK3 thus may account in part for their therapeutic action in bipolar disorder (Rao et al. Abstr. Biol Psychiatry, 63:1S-301S, 60S, 2008)